Neurotrophin Peptidomimetics: A new era in precision neurology and drug development

Neurotrophins are a critical family of growth factors that significantly influence the survival, development, and maintenance of neurons in the nervous system. Key members, including Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Neurotrophin-3 (NT-3), play essential roles in neuronal health and function. However, their therapeutic application is limited by challenges such as poor bioavailability, instability, and difficulty in crossing the blood-brain barrier. To address these limitations, peptidomimetics have emerged as promising synthetic alternatives designed to mimic the biological activity of neurotrophins while enhancing stability and specificity. This review provides a comprehensive exploration of neurotrophin peptidomimetics, detailing their design principles, mechanisms of action, and therapeutic applications across various disease areas, including neurodegenerative diseases, cardiovascular disorders, oncology, infectious diseases, and autoimmune conditions. We discuss the innovative strategies employed in the development of peptidomimetics and highlight their potential to overcome existing pharmacological constraints associated with natural neurotrophins. Furthermore, we examine the challenges and limitations faced in the field, including stability issues and clinical translation hurdles. Finally, we outline future directions for research that may enhance the efficacy and applicability of neurotrophin peptidomimetics in clinical settings. By synthesizing current findings, this review aims to illuminate the transformative potential of these compounds in addressing unmet medical needs in neurology and beyond.